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Publication numberUS5158676 A
Publication typeGrant
Application numberUS 07/617,755
Publication dateOct 27, 1992
Filing dateNov 26, 1990
Priority dateMay 25, 1990
Fee statusLapsed
Also published asDE4016760A1, EP0458188A1
Publication number07617755, 617755, US 5158676 A, US 5158676A, US-A-5158676, US5158676 A, US5158676A
InventorsKlaus Kreher, Gerhard Munch, Ernst Rogler
Original AssigneeMerck Patent Gesellschaft Mit Beschrankter Haftung
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Chromatography apparatus
US 5158676 A
Abstract
Chromatography systems with devices for compressing the column packing and/or for pulsation damping have incorporate an additional device in which a preselected minimum pressure, which is independent of the eluent pressure, is combined with a second pressure component which is proportional to the eluent pressure.
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Claims(6)
What is claimed is:
1. Apparatus for axially compressing packing is a chromatography column into which an eluent is introduced under pressure, the apparatus comprising:
a piston disposed within the column adjacent one end of the column;
means in communication with the column for introducing the eluent into the column;
means for applying pressure to the eluent;
an eluent line connecting the pressure applying means and eluent introducing means to one another
force applying means connected to the piston for urging the piston to axially pressurize the packing and eluent in the column;
hydraulic pressurizing means connected by a hydraulic line to the force applying means, and
pressure transmitting means connecting the hydraulic line to the eluent line.
2. The apparatus of claim 1 wherein the pressure transmitting means comprises a cylinder having first and second faces, the first face having an area larger than the second face, thereon defining first and second chambers within the cylinder with the first chamber connected to the eluent line and the second chamber connected to the hydraulic line.
3. The apparatus of claim 2 wherein the hydraulic line includes a check valve therein which closes when the pressure in the eluent line exceeds a predetermined pressure.
4. The apparatus of claim 3 further including pressure transferring means disposed between the eluent line and the first chamber of the pressure transmitting means.
5. The apparatus of claim 1 wherein the hydraulic line includes a check valve therein which closes when the pressure in the eluent line exceeds a predetermined pressure.
6. The apparatus of claim 5 further including pressure transferring means disposed between the eluent line and hydraulic line.
Description
BACKGROUND OF THE INVENTION

The invention relates to novel, improved chromatography apparatus and methods consisting, as a minimum, of a chromatography column with a device for the axial compression of the column packing and/or of a pulsation-damping device and of an elution device.

In chromatographic separations of substances, especially in liquid chromatography, different pressures for the supply of eluent are necessary, depending on the desired flow rate, the viscosity of the eluent and the resistance to flow of, in particular, the separating column.

The operation of the varying operating pressures on the separating material in the column leads to stress thereon, so that the reproducibility of separation runs and the useful life of the column material may both deteriorate.

One method for solving this problem is disclosed in EP 0 271 378: the eluent provides, with its own pressure via a pressure-transmission arrangement and a device for compressing the separation material, the required backpressure which automatically adjusts to the operating state of the chromatography system. However, this compressive pressure collapses on switching the system off or on malfunctioning of the eluent pump. This results in the separating material in the column continuing to be mechanically stressed in a disadvantageous manner by consecutive compression and relaxation modes.

Another problem is that the operation of eluent pumps is not free of pulsations so that this too results in a mechanical stress on the complete system. The pulsation-damping devices employed for damping the pressure pulses operate only in a very narrow pressure range and thus lose efficacy under varying operating conditions. This is because the pressure of the eluent may vary within wide limits (about 10 to 250 bar).

It has now been found that improved chromatography systems can be provided in which a pressure composed of two components is applied to constructional elements such as a compression or a pulsation damping device. One of these two pressure components is proportional to the eluent pressure and the additional one is a constant minimum pressure.

SUMMARY OF THE INVENTION

Hence, the invention relates to chromatography systems at least consisting of a chromatography column with a device for the axial compression of the column packing and/or of a pulsation-damping device and of an elution device, characterized in that additionally provided is a means which combines a preselected minimum pressure, which is independent of the eluent pressure, with a second pressure component which is proportional to the eluent pressure.

It has been found that the object can be achieved according to the invention by exposing the working medium, for example hydraulic oil or a gas such as air to a pressure-transmission means, and additionally allowing a means for generating a constant pressure, for example a pump or a spring-tensioned movable piston in a cylinder, to act.

The invention additionally relates to chromatographic separation methods characterized in that the chromatography system according to the invention is used.

BRIEF DESCRIPTION OF THE DRAWINGS

Various other objects, features and attendant advantages of the present invention will be more fully appreciated as the same becomes better understood when considered in conjunction with the accompanying drawings, in which like reference characters designate the same or similar parts throughout the several views, and wherein:

FIG. 1 is a schematic view of a first embodiment of the invention showing a device for axial compression of the column packing comprising a pressure transmission device together with a pump with a check valve and a reservoir for hydraulic fluid as generating means for the constant pressure component;

FIG. 2 is a view similar to FIG. 1 but utilizing a hydraulic cylinder as generating means for the constant pressure component;

FIG. 3 is a view similar to FIG. 1 of a second, preferred embodiment of the invention employing a pressure transfer device in combination with a pressure transmission device;

FIG. 4 is a schematic view of a third embodiment of the invention wherein a pulsation-damping device is employed in combination with a pressure transmission device;

FIG. 5 is a schematic view of a fourth embodiment of the invention similar to FIG. 4 wherein a pulsation damping device is employed with a combination of a pressure transfer device and a pressure transmission device; and

FIG. 6 is a fifth embodiment of the invention utilizing a common pressure-transfer device for both a compression and pulsation device.

DETAILED DESCRIPTION

A chromatography system according to the invention is depicted in FIGS. 1 and 2 and contains essentially the following elements: at least one pressure-transmission device (1) which transfers the pressure of the eluent (2) with a suitable transmission ratio to a hydraulic fluid (3) so that the force acting on the piston of the compression arrangement (8) is a factor in the region of 1.05 to 1.6, preferably 1.2-1.4, greater than the force effective on the eluent side. As long as the pressure on the pressure transmitter on the side of the hydraulic oil is less than the preselected compressive pressure, a device provides a constant pressure. Various devices of this type are known in the prior art and can be employed according to the invention. As an example of such devices, FIG. 1 shows a pump (4) with a check valve (5) and a reservoir for hydraulic fluid (25). FIG. 2 shows as another example a cylinder (6) with movable piston (7) which is subject to an adjustable spring tension. The chromatography column is identified by (22), the elution pump by (23) and the eluent reservoir by (24).

In each case, a device of this type provides a selected minimum compressive pressure. If the eluent pressure increases so that the pressure on the pressure transmitter (1) on the side of the hydraulic oil is greater than the preselected compressive pressure, the check valve (5) closes and the required increase compressive pressure is applied to the column packing.

A preferred embodiment of the chromatography system according to the invention is depicted in FIG. 3. In this case, a pressure-transfer device (9) is additionally inserted between the eluent (2) and the pressure-transmission device (1). The former transfers the pressure of the eluent (2) to a hydraulic fluid (10) which is separated from the eluent by a solvent-resistant and elastic diaphragm (11).

This preferred embodiment has other important advantages over the state of the art as disclosed, for example, in the publication EP 0 271 378: the dead volume on the eluent side is considerably reduced, in addition the eluent flows through the pressure-transfer arrangement. This is why when the eluent is changed, for example in the frequently used gradient elution, no disturbances of the gradient due to mixing occur. Moreover, diaphragms of this type are more resistent to the eluents used and, in addition, exhibit leaks less often than is the case with sliding seals.

In another embodiment of the invention as depicted in FIG. 4, a pulsation-damping device (12) is equipped with a pressure-transmission device (13). The latter transfers the pressure of the eluent (2) to a gas, for example air (14) , with which a chamber (15) of the pulsation damper is filled. Additionally present is a device for generating a constant pressure, for example compressor (16) with a check valve (17), in order to provide the chamber (15) of the pulsation-damping device with a minimum pressure.

A preferred embodiment of the arrangement described last (see FIG. 5) contains an additional pressure-transfer device (18) which transfers the pressure of the eluent (2), using a solvent-resistent and elastic diaphragm (19), to a hydraulic fluid (20). The latter transfers the pressure via the pressure-transmission device (13) to the air (14) with which the chamber (15) of the pulsation-damping device (12) is filled.

In another possible embodiment (see FIG. 6), a common pressure-transfer device (21) serves for both arrangements: both for the compression device and for the pulsation damping device.

Without further elaboration, it is believed that one skilled in the art can, using the preceding description, utilize the present invention to its fullest extent. The following preferred specific embodiments are, therefore, to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever.

The entire disclosures of all applications, patents and publications, cited above and below, and of corresponding application Federal Republic of Germany P 40 16 760.7, filed May 25, 1990, are hereby incorporated by reference.

From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.

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Reference
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Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US5610322 *Sep 13, 1995Mar 11, 1997Hoechst AktiengesellschaftDevice for packing chromatography columns
US5667675 *Feb 29, 1996Sep 16, 1997Varian Associate, Inc.Collapsible apparatus for compressing packing material in liquid chromatography columns and methods of use
US5919361 *Dec 17, 1997Jul 6, 1999Uop LlcSpring-loaded hydraulically active liquid chromatography column
US6001260 *Jun 3, 1997Dec 14, 1999Varian Associates, Inc.Collapsible apparatus for compressing packing material in liquid chromatography columns and methods of use
US6190560 *Sep 30, 1999Feb 20, 2001Mann Welding CompanySlurry fill method and valve
US6558539 *Nov 14, 2000May 6, 2003William H. MannSlurry fill method and valve
US7132053Apr 9, 2002Nov 7, 2006NovasepProtective device for the chromatographic bed in dynamic axial compression chromatographic columns
US7169307 *Sep 2, 2004Jan 30, 2007Jian LiuProcess for the extraction of paclitaxel and 9-dihydro-13-acetylbaccatin III from Taxus
US7238282 *Mar 4, 2005Jul 3, 2007Millipore CorporationSystem for automated compression of chromatography columns
US7671203Feb 18, 2003Mar 2, 2010Mallinckrodt Inc.Method and system for separation and purification of at least one narcotic alkaloid using reverse phase preparative chromatography
US7767090 *Nov 27, 2006Aug 3, 2010Millipore CorporationSystem for automated compression of chromatography columns
US8591742Jun 18, 2010Nov 26, 2013Emd Millipore CorporationSystem for automated compression of chromatography columns
US20040099604 *Apr 9, 2002May 27, 2004Wilhelm HauckProtective device for the chromatographic bed in dynamic axial compression chromatographic columns
US20050182257 *Feb 18, 2003Aug 18, 2005Antonini Enrico A.Method and system for separation and purification of at least one narcotic alkaloid using reverse phase preparative chromatography
US20060043020 *Sep 2, 2004Mar 2, 2006Sunrise Biosciences Inc.Process for the extraction of paclitaxel and 9-dihydro-13-acetylbaccatin III from Taxus
US20060196832 *Mar 4, 2005Sep 7, 2006Jeremy PerreaultSystem for automated compression of chromatography columns
US20100256925 *Jun 18, 2010Oct 7, 2010Millipore CorporationSystem for automated compression of chromatography columns
US20100312480 *Apr 23, 2010Dec 9, 2010Hansteen FredrikMethod for monitoring fluid flow in a multi-layered system
WO2002084275A1 *Apr 9, 2002Oct 24, 2002Jean BlehautProtective device for the chromatographic bed in dynamic axial compression chromatographic columns
Classifications
U.S. Classification210/198.2, 96/101, 210/656, 210/349
International ClassificationG01N30/60, G01N30/32, G01N30/52, B01D15/08, G01N30/36
Cooperative ClassificationG01N30/6021, G01N2030/322, G01N30/36, G01N30/52, G01N2030/522
European ClassificationG01N30/36, G01N30/52
Legal Events
DateCodeEventDescription
Nov 26, 1990ASAssignment
Owner name: MERCK PATENT GESELLSCHAFT MIT BESCHRANKTER, GERMAN
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST.;ASSIGNORS:KREHER, KLAUS;MUNCH, GERHARD;ROGLER, ERNST;REEL/FRAME:005519/0984
Effective date: 19901116
Jun 4, 1996REMIMaintenance fee reminder mailed
Oct 27, 1996LAPSLapse for failure to pay maintenance fees